Chenodiol

▲8月1-2日 2025生物医药创新博览会 扫码报名注：本文不构成任何投资意见和建议，以官方/公司公告为准；本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及），不代表平台立场。任何文章转载需得到授权。在生物制药领域，时常上演着跌宕起伏的故事，而Mike Grey拯救“我”（本文代指Maralixibat）的经历无疑是其中扣人心弦的篇章。“药”途新篇章Mike Grey在制药行业堪称一位经验丰富的老将，拥有40年的深厚积淀。他曾在多家公司担任高级职位，如SGX Pharmaceuticals的总裁兼首席执行官（该公司于2008年被礼来公司收购）、Trega Biosciences的总裁兼首席执行官（2001年被Lion Bioscience收购）以及Biochem Therapeutic的总裁等。2011~2014年期间，他担任Lumena的总裁兼首席执行官，而这段经历为后来“我”的新主人Mirum Pharmaceuticals管线的发展埋下了伏笔。Mike Grey2014年Shire（已被武田收购）以2.6亿美元的价格收购Lumena Pharmaceuticals时获得了Maralixibat（当时代号为LUM001），彼时Shire对“我”寄予厚望，期望能在罕见肝病治疗领域有所建树，然而后续的研发进程却遭遇重创，“我”就此陷入长达4年的“冷冻期”。药融云数据，www.pharnexcloud.com；改名后为摩熵医药数据：药品研发信息2018 年，Mike Grey创立了Mirum Pharmaceuticals，且在放弃对该药物的控制4年后，凭借新的顶线数据，成功从Shire获得了“我”的全球独家许可权，并继续进行研究。Mirum Pharmaceuticals也由此开启了在罕见病药物研发领域的征程。凭借这一成果，公司募集到1.2亿美元的A轮融资，为公司后续发展注入了强大动力。起死回生之后的“开挂药生”1、为ALGS和PFIC患者瘙痒按下“暂停键”“我”的商品名叫LIVMARLI，是一种口服、每日一次的回肠胆汁酸转运蛋白（IBAT）抑制剂，其作用机制是通过阻断胆汁酸肠肝循环，降低肝内和血清中的胆汁酸水平，进而减少由此介导的肝脏损伤，缓解瘙痒症状。在适应症方面，“我”是首款获批用于治疗Alagille综合征（ALGS）患者胆汁淤积性瘙痒症的药物。在美国用于3个月及以上ALGS患者的胆汁淤积性瘙痒症；欧盟用于2个月及以上ALGS患者的胆汁淤积性瘙痒症；在加拿大用于1岁~18岁ALGS患者的胆汁淤积性瘙痒；在中国、以色列和韩国用于1岁及以上 ALGS患者的胆汁淤积性瘙痒症，其中，在中国由北海康成商业化，以色列由Neopharm商业化，韩国由GC Pharma商业化。另外，“我”还被FDA批准用于治疗12个月及以上的进行性家族性肝内胆汁淤积症（PFIC）患者的胆汁淤积性瘙痒症，并在欧盟获批用于治疗3个月及以上年龄的PFIC患者。公司目前在推进“我”用于其他适应症。通过名为EXPAND的临床试验3期研究，正在探索ALGS、PFIC、PSC、妊娠肝内胆汁淤积症和PBC以外的罕见胆汁淤积环境中瘙痒的治疗，预计2026年完成该试验的招募。2、从旧疾治疗到CTX新疗法的研发华丽转身Mirum Pharmaceuticals其他获批产品CTEXLI（chenodiol）片剂也称为鹅脱氧胆酸（CDCA），是一种天然存在的胆酸，最初被批准用于治疗胆囊中放射性不透明结石患者，Mirum Pharmaceuticals发现其在治疗脑腱黄瘤病（CTX）方面具有潜力。其作用机制是通过补充患者体内缺乏的胆汁酸，助力清除有毒的胆固醇代谢物沉积，从而有效缓解CTX相关的临床症状。CTX是一种极为罕见的遗传代谢性疾病，由于CYP27A1基因突变，致使人体分解脂肪的关键酶出现缺乏。若得不到及时有效的治疗，患者将饱受慢性腹泻、青少年双侧白内障、肌腱黄瘤以及神经功能恶化等症状的折磨。2024年6月，MirumPharmaceuticals向FDA提交了chenodiol用于治疗CTX患者的NDA，NDA的提交主要基于名为RESTORE的临床试验3期研究的结果，该研究评估了chenodiol在成人CTX患者中的效果，研究达到了主要终点，即患者的胆汁醇水平减少具有高度统计学显著性（p<0.0001）；在随机双盲停药期结束时，安慰剂与chenodiol组之间的胆汁醇差异高达20倍；RESTORE研究还表明，chenodiol治疗也显著改善患者的血清胆固烷醇水平。2025年2月21日，FDA正式批准chenodiol上市，用于治疗成人CTX，为CTX患者带来了新的希望曙光，也标志着公司在罕见病治疗领域的又一重大突破。3、从Asklepion到Mirum，一路为罕见病患者护航另一个产品CHOLBAM（胆酸胶囊）最开始由Asklepion Pharmaceuticals研发，2015年3月获批上市；2015年Retrophin从Asklepion Pharmaceuticals收购了Cholbam；Mirum Pharmaceuticals后来又从Retrophin手中收购了包括Cholbam在内的胆汁酸产品组合。Cholbam主要用于治疗者因单一酶缺陷导致胆汁酸合成障碍的儿童和成人患者，同时也可作为过氧化物酶体疾病（包括PBD-ZSD）患者的辅助治疗药物。它通过补充患者体内缺乏的胆酸，调节胆汁酸代谢平衡，从而改善相关症状。目前Cholbam已在市场上稳定销售，为相关罕见病患者提供了有效的治疗选择，在胆汁酸合成障碍及过氧化物酶体疾病治疗领域占据了一定的市场份额，为公司带来了持续的收入流。深耕胆汁淤积，剑指FXS：药物新势力各展锋芒1、Volixibat以差异特性攻PSC、PBC胆汁淤积之垒Volixibat是一种口服、最低吸收药物，同样旨在抑制IBAT，其作用机制与LIVMARLI类似，但在药物特性上有所差异，有望为不同患者群体提供更合适的治疗选择。目前正在两项临床试验2b期研究中进行评估，包括原发性硬化性胆管炎（PSC）的VISTAS试验和原发性胆汁性胆管炎（PBC）中的VANTAGE试验。PSC是一种严重的特发性慢性胆汁淤积性肝病，其特征是胆管进行性炎症和破坏，可导致危及生命的并发症，高达65%的PSC患者在病程中患有瘙痒症。VISTAS试验是一项适应性、随机研究，旨在评估Volixibat对PSC和瘙痒患者瘙痒、sBA和纤维化标志物的影响，预计在2025年第三季度完成入组，2026年第二季度获得顶线数据。PBC是一种慢性、罕见的胆汁淤积性肝病，其特征是免疫介导的肝内胆管破坏引起的进行性肝胆汁血流障碍，这会导致肝脏胆汁酸浓度增加，从而导致肝脏局部炎症反应，进展为肝纤维化、肝硬化和肝功能失代偿。VANTAGE研究预计在2026年完成入组。2、MRM-3379借PDE4D抑制破FXS神经障碍之防MRM-3379是一种选择性PDE4D抑制剂，正在推进用于治疗FXS（脆性X综合征）。FXS是一种由FMR1基因异常导致的遗传性疾病，主要是由于FMR1基因的5'端非翻译区存在CGG重复序列异常扩增，使得FMR1基因沉默，无法产生正常的脆性X智力低下蛋白，进而影响神经元的正常发育和功能，导致一系列的认知、行为和神经发育障碍症状。PDE4D在大脑中对学习、记忆和情绪调节等非常重要的区域高度活跃，会分解（cAMP），而cAMP是神经细胞之间的一种关键信号分子，FXS患者的cAMP水平低于正常水平。MRM-3379可选择性地抑制PDE4D的活性，从而增加大脑中的cAMP水平，有助于重建受该疾病影响的大脑神经细胞通讯网络，进而可能缓解FXS的症状。预计今年会启动MRM-3379的临床试验2期研究。现金储备雄厚，销售额飙升领航新程5月7号，“我”的主人Mirum Pharmaceuticals报道了今年第一季度的营收情况，截止2025年3月31日，公司拥有不受限制的现金、现金等价物和投资2.986亿美元。发稿前市值约合22亿美元。2025年第一季度公司全球产品净销售额为1.116亿美元，上年同期只有6890万美元，其中“我”的净销售额为7320万美元，胆汁酸药物产品净销售额2840万美元。总运营支出为1.268亿美元，上年同期为9570万美元。根据上一年统计，2024年全年产品净销售额为3.364亿美元，上年同期1.789亿美元，2024年度“我”的净销售额共计2.133亿美元，胆汁酸药物产品净销售总额1.231亿美元。2024年度全年总运营支出为4.245亿美元，包括7940万美元的非现金股票薪酬、无形摊销和其他非现金支出。参考：NMPA/CDE；摩熵医药数据库，https://pharma.bcpmdata.com/；FDA/EMA/PMDA；相关公司公开披露（除标注外，正文图片均来自企业官网）；https://mirumpharma.com/；https://ir.mirumpharma.com/news-events/News/default.aspx；https://mp.weixin.qq.com/s/z_yhy3cckqanVeqldP3bvg；https://www.takeda.com/newsroom/shire-news-releases/2015/shire-reports-topline-results-from-phase-2-studies-in-children-with-alagille-syndrome/；等等。此文仅用于向医疗卫生专业人士提供科学信息，不代表平台立场，不作任何用药推荐。更多药企信息交流可后台留下名片。提前预约，扫码报名参加8月峰会植根上海、辐射全球,药融圈作为生物医药产业级战略平台,以"让智慧与人脉无界流动"为使命,构建覆盖药物研发、生产、流通、商业化的全产业链赋能体系。通过智能化云服务、精准资源链接、产业智库与生态社群四大核心引擎,打造中国医药价值流动的基础设施。在全球化与数字化双重浪潮下,药融圈正重新定义医药资源的流通范式--这里不仅是信息与人脉的枢纽站,更是催生产业变革的化学反应器。我们以中国为原点,编织全球医药智慧网络,让每一次精准链接都成为企业跨越式增长的催化剂。点点赞点分享点推荐

- 28-week data from the Phase 2b VANTAGE PBC study highlights statistically significant improvements in pruritus and numeric improvements in fatigue, the two most burdensome symptoms of PBC - Seventy percent of patients treated with volixibat experienced a ≥50% reduction in serum bile acids - Volixibat treated patients experienced reductions in IL-31 FOSTER CITY, Calif.--(BUSINESS WIRE)-- Mirum Pharmaceuticals, Inc. (NASDAQ: MIRM) today presented new data from its Phase 2b VANTAGE study at the European Association for the Study of the Liver (EASL) meeting in Amsterdam, the Netherlands. The VANTAGE study is evaluating volixibat in patients with cholestatic pruritus caused by primary biliary cholangitis (PBC). “The extended VANTAGE analysis provides encouraging insights into the potential impact that volixibat may have in treating the most severe and bothersome symptoms for patients living with PBC, including pruritus and fatigue,” said Joanne Quan, MD, chief medical officer at Mirum. “We are also encouraged by the reductions seen in IL-31 in conjunction with sBA reductions, showing the potential for volixibat treatment to help alter the inflammatory condition present in PBC.” Data from the interim analysis of VANTAGE were highlighted with new analyses through week 28. Patients were randomized to receive volixibat 20mg BID, 80mg BID, or placebo BID. The primary endpoint of the study was mean change in weekly averaged daily itch score, as measured by the adult ItchRO scale, from baseline to Week 17-Week 28. Volixibat treatment led to rapid (as early as week 1) and sustained reductions in ItchRO with the volixibat combined dose group achieving a statistically significant 3.78-point reduction from Baseline (p<0.0001) and a placebo-adjusted response of 2.51 (p=0.0004). Each volixibat dose achieved statistically significant and similar responses (20mg BID: -2.4 [P=0.0039]; 80mg BID: -2.6 [P=0.0010]). The analysis also provided data across secondary endpoints showing reductions in serum bile acids (sBA) and quality of life (QoL) measures. Overall, 70% of patients who received volixibat achieved ≥50% reduction in sBA. Further, the data showed improvement from baseline in health-related quality of life, including fatigue and sleep, for patients treated with volixibat. Reductions from baseline were observed in inflammatory biomarker IL-31 in patients treated with volixibat. No new safety signals were observed, and adverse events were similar between the 20 mg and 80 mg treatment groups. The most common adverse event was diarrhea (77%) with all cases mild to moderate; one case resulted in discontinuation. Given the similar results with both efficacy and safety between the 20mg BID and 80mg doses BID, the 20mg BID dose was selected for the confirmatory portion of the VANTAGE study. To view the presentation, please visit the Publications & Presentations on Mirum’s website. About the VANTAGE Study VANTAGE is a randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of volixibat in patients with pruritus caused by primary biliary cholangitis (PBC). Patients were randomized to receive volixibat 20mg BID (n=10), 80mg BID (n=10), or placebo BID (n=11). The primary endpoint of the study was mean change in weekly averaged daily itch score, as measured by the adult ItchRO scale (an 11 point scale where 0 = no itch and 10 = worst itch imaginable), from baseline to Week 17-Week 28. VANTAGE is designed as a two-part study: the first part is intended to confirm dose (completed) and the second intended to be the confirmatory portion (currently enrolling patients). In the first part of the study, patients were randomized to receive either volixibat 20mg BID, 80mg BID, or placebo BID; the second part of the study randomized patients to receive either volixibat 20mg BID (the selected dose based on part one) or placebo BID. About Primary Biliary Cholangitis Primary Biliary Cholangitis (PBC) is a chronic, progressive, immune-mediated condition leading to the destruction of small intrahepatic bile ducts. The disease impacts an estimated 230,000 patients in the United States and the European Union, with women predominantly affected (a sex ratio of 9:1). Key clinical features and symptoms include cholestatic pruritus, fatigue, sicca syndrome, abdominal pain, cirrhosis, and hepatocellular carcinoma. Cholestatic pruritus (itch) and fatigue are two of the most debilitating symptoms and greatly affect overall health-related quality of life (HRQoL). Cholestatic pruritus can affect up to 80% of individuals and is thought to result in part from accumulation of toxic bile acids. About Volixibat Volixibat is an oral, minimally absorbed agent designed to selectively inhibit the ileal bile acid transporter (IBAT). Volixibat may offer a novel approach in the treatment of adult cholestatic diseases by blocking the recycling of bile acids, through inhibition of IBAT, thereby reducing bile acids systemically and in the liver. Volixibat is currently being evaluated in Phase 2b studies for primary sclerosing cholangitis (PSC) (VISTAS study), and primary biliary cholangitis (PBC) (VANTAGE study). In June, Mirum announced positive interim results from the Phase 2b VANTAGE study showing statistically significant improvement in pruritus as well as reductions in serum bile acids and improvements in fatigue for patients treated with volixibat. No new safety signals were observed, and the most common adverse event was diarrhea with all cases mild to moderate. Volixibat has been granted breakthrough therapy designation for the treatment of PBC. About LIVMARLI® (maralixibat) oral solution and LIVMARLI® (maralixibat) tablets LIVMARLI® (maralixibat) is an orally administered, ileal bile acid transporter (IBAT) inhibitor approved by the U.S. Food and Drug Administration for two pediatric cholestatic liver diseases, in both liquid and tablet formulations. It is approved for the treatment of cholestatic pruritus in patients with Alagille syndrome (ALGS) in the U.S. three months of age and older and in Europe for patients two months of age and older. It is also approved in the U.S. for the treatment of cholestatic pruritus in patients with progressive familial intrahepatic cholestasis (PFIC) 12 months of age and older and in Europe for the treatment of PFIC in patients three months of age and older. For more information for U.S. residents, please visit LIVMARLI.com. LIVMARLI is currently being evaluated in the Phase 3 EXPAND study in additional settings of cholestatic pruritus. To learn more about ongoing clinical trials with LIVMARLI, please visit Mirum’s clinical trials section on the company’s website. U.S. IMPORTANT SAFETY INFORMATION Limitation of Use: LIVMARLI is not for use in PFIC type 2 patients who have a severe defect in the bile salt export pump (BSEP) protein. LIVMARLI can cause side effects, including: Liver injury. Changes in certain liver tests are common in patients with Alagille syndrome and PFIC but can worsen during treatment. These changes may be a sign of liver injury. In PFIC, this can be serious or may lead to liver transplant or death. Your healthcare provider should do blood tests and physical exams before starting and during treatment to check your liver function. Tell your healthcare provider right away if you get any signs or symptoms of liver problems, including nausea or vomiting, skin or the white part of the eye turns yellow, dark or brown urine, pain on the right side of the stomach (abdomen), bloating in your stomach area, loss of appetite or bleeding or bruising more easily than normal. Stomach and intestinal (gastrointestinal) problems. LIVMARLI can cause stomach and intestinal problems, including diarrhea and stomach pain. Your healthcare provider may advise you to monitor for new or worsening stomach problems including stomach pain, diarrhea, blood in your stool or vomiting. Tell your healthcare provider right away if you have any of these symptoms more often or more severely than normal for you. A condition called Fat Soluble Vitamin (FSV) Deficiency caused by low levels of certain vitamins (vitamin A, D, E, and K) stored in body fat is common in patients with Alagille syndrome and PFIC but may worsen during treatment. Your healthcare provider should do blood tests before starting and during treatment and may monitor for bone fractures and bleeding which have been reported as common side effects. LIVMARLI is available in oral solution or tablet formulations and is taken by mouth 30 minutes before a meal. For Alagille syndrome, LIVMARLI is taken one time each day in the morning. For PFIC, LIVMARLI is taken two times each day. If you take the oral solution, use the oral dosing dispenser to measure your dose. US Prescribing Information EU SmPC Canadian Product Monograph About Mirum Pharmaceuticals, Inc. Mirum Pharmaceuticals, Inc. is a biopharmaceutical company dedicated to transforming the treatment of rare diseases affecting children and adults. Mirum has three approved medications: LIVMARLI® (maralixibat) oral solution/LIVMARLI® (maralixibat) tablets, CHOLBAM® (cholic acid) capsules, and CTEXLI™ (chenodiol) tablets. LIVMARLI, an IBAT inhibitor, is approved for the treatment of two rare liver diseases affecting children and adults. It is approved for the treatment of cholestatic pruritus in patients with Alagille syndrome in the U.S. (three months and older), in Europe (two months and older), and in other regions globally. It is also approved in the U.S. in cholestatic pruritus in PFIC patients 12 months of age and older; in Europe, it is approved for patients with PFIC three months of age and older. Mirum has initiated the Phase 3 EXPAND study, a label expansion opportunity for LIVMARLI in additional settings of cholestatic pruritus. CHOLBAM is FDA-approved for the treatment of bile acid synthesis disorders due to single enzyme deficiencies and adjunctive treatment of peroxisomal disorders in patients who show signs or symptoms of liver disease. CTEXLI is FDA-approved for the treatment of cerebrotendinous xanthomatosis (CTX) in adults. Mirum's late-stage pipeline includes two investigational treatments for several rare diseases. Volixibat, an IBAT inhibitor, is being evaluated in two potentially registrational studies including the Phase 2 VISTAS study for primary sclerosing cholangitis (PSC) and Phase 2b VANTAGE study for primary biliary cholangitis. Volixibat has been granted Breakthrough Therapy Designation for the treatment of cholestatic pruritus in patients with PBC. Mirum is also planning for a Phase 2 study evaluating MRM-3379, a PDE4D inhibitor for the treatment of Fragile X syndrome, a rare genetic neurocognitive disorder. To learn more about Mirum, visit mirumpharma.com and follow Mirum on Facebook, LinkedIn, Instagram and Twitter (X). Forward-Looking Statements Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include statements regarding, among other things, data from Mirum’s volixibat studies, including the VANTAGE study of volixibat in patients with pruritus due to PBC and such implications for patients in real world settings. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Words such as “will,” “could,” “can,” “would,” “potential,” “hope,” “opportunity,” and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon Mirum’s current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, risks and uncertainties associated with Mirum’s business in general, the impact of macroeconomic and geopolitical developments, and the other risks described in Mirum’s Annual Report on Form 10-K for the year ended December 31, 2024, filed with the U.S. Securities and Exchange Commission on February 26, 2025, and subsequent filings with the U.S. Securities and Exchange Commission, which are available at www.sec.gov. All forward-looking statements contained in this press release speak only as of the date on which they were made and are based on management’s assumptions and estimates as of such date. Mirum undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by law. Media Contact: Erin Murphy media@mirumpharma.com Investor Contact: Andrew McKibben ir@mirumpharma.com